The purpose of the synthesis core facility is to provide the following to Projects II, III and IV: 1) routine synthesis of individual compounds of iterations from synthetic combinatorial libraries based on protocols produced during the development of those libraries in Project I; and 2) resynthesis of synthetic combinatorial libraries to replenish inventory. The use of trained technicians to perform this work is an efficient and cost effective way to accomplish this work, which is more routine than initial development of the library. The proposed core facility is an expansion of an existing facility located within the laboratories of Torrey Pines Institute for Molecular Studies, the applicant organization. This facility will be able to output between 300 to 500 compounds per month, depending on the complexity of the particular synthetic reaction schemes used, as well as provide analytical and purification services. The facility's primary function will be to synthesize individual defined compounds based on the results of screening the positional scan formatted synthetic combinatorial libraries. Secondary, functions will include the synthesis of sub-libraries based on the iterative deconvolution method as necessary, and synthesis and purification of individual compounds as necessary. It is expected that in the later portion of this program project the resynthesis of depleted libraries will be required. The synthesis core facility will be located at Torrey Pines Institute for Molecular Studies and will occupy 1,300 square feet of assigned space. Routine solid phase synthesis will be carried out using the simultaneous multiple synthesis technique developed by the principal investigator (tea- bag method). This laboratory contains a full complement of equipment necessary for organic synthesis. The available analytical/purification equipment include: 1H and 13C NMR, LC-MS, MALDI-MS, analytical and preparative HPLCs, and HPCE.